Update on TIVA

Bekele, ACA
HUCSH, 2023 1
Objective of the presentation

To discuss :

• Update in TIVA and its practical aspects

• Journal Articles & Guidelines

• Clinical Uses and future practices of TIVA

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Lecture Outline
• Introduction to TIVA Practice

• Drugs selection and its combination

• Methods of TIVA delivery

• Journal articles and guidelines

• TIVA in special population

• Promising of TIVA

• Summary
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TIVA: Optional or Required?

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 WHY TIVA ?
• Necessity

• Benefits

• choice

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 Introduction
• TIVA is technique of • Become Popular, Practical and
Possible due to:
Anesthesia given
exclusively by the IV 1. The advance knowledge of Pk and
route/ without Gas PD properties of newly developing
drugs
Anesthesia
Miller’s 9 2. New concepts in PK modelling
edition coupled with advances in the
technology of infusion pumps
(Stoelting’s Basic anest 6th ed)

3. Current Global issues (WAG vs. Health

policy: carbon free footprint) US Narrative
Review . Anesth 2021
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 TIVA...

• With/Without Airway Equipments

• With Single and/ or Combined drugs

• With/Without Regional analgesia ( MAC)

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 Almost in all
surgical
procedures

Daycare Surgery,
MH susceptible
Patient Choice

Short
procedures: CT, TIVA Remote
MRI, Cardiac,
catheterisation INDICATIONS locations

Neurosurgery Airway
Neuro monitoring procedures

PONV risk
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Advantages
• Clinical Benefit of TIVA
• Predictable onset and offset of anesthetic effect
• More HD stability and shorter recovery
•
• Economic Benefits of TIVA
• Costs and Hospital stay

• Environmental friend! (Safe)

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TIVA Drugs
• All most all IV
anesthetics but shorter
context sensitivity half
time agents are preferred

• CSHT- Time taken for

plasma conc- of a drug
to decline by 50% after
an infusion designed to
maintained steady state.
(R.Eyres 2014) 10
BET Principle
(3 compartment model)

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12
 TIVA Drugs combinations
•KETOFOL TIVA (Ketamine and Propofol) Amorytin,et.al 2014

•Higher Ketamine ratio 1:2 is useful for induction and lower for mtc.

•RP TIVA (Remefentanyl and Propofol) Ideal combination for TCI

•PDF TIVA (Propofol, Dexmedetomidine and Fentanyl)

•KPD TIVA (Ketamine, Propofol and Dexmedetomidine) Ragia et.al 2012

Best opioid free Tiva

•KETODEX TIVA (Ketamine and Dexmedetomidine) Vidya Sagar 2017

•Opioid free anesthesia, preferable to children, obesity 13

Ketofol journal articles
• Amorytin S(2014) Ketofol: A
combination of ketamine and
propofol. J. Anesth critical care
open Access 1(5).00031
(Thailand)
• Conclusion: ketofol has several
benefits of HD stability, lack of
respiratory depression, good
recovery and post op analgesia.
• The safety and efficacy of
ketofol as analgesics are depend
on dose and ratio of mixtures .
• Saudi J Anest 2016 Aug4(2).
72-79
• Comparison of two drug
combination in tiva: ketofol
and propofol-fentanyl;
• Conclusion: the result of this
study suggest that both
ketamine-propofol and
fentanyl-propofol combination
produce rapid, pleasant and
safe anesthesia with only few
unwanted side effects and
minor HD fluctuations 14
Ketodex Journal articles
• Comparison of ketamine and dexmedtomidine versus
ketamine propofol for procedural sedation in children
undergoing minor cardiac catetherasation.
Ann.Card. Anesth.Oct 2017;20(4).422-25
• Conclusion: use of Ketodex combination is safe
alternative, without any HD and respiratory effect during
cardiac catheterization procedure but with some delay
recovery

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Propofol + Remifentanil (Remifol)

• Most widely used TIVA combination

• Adequate analgesia, satisfactory hemodynamic, rapid recovery

• Remifentanil concentration is 50 mcg/ml (1mg in 20 ml propofol)

• Synergism- Propofol dose reduction by 50%

• Delivered either by conventional pumps or by TCI systems or by

close loop systems

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• Ideal agents for TCI model
PR TIVA...

• Journal in article (Guener junior,et.al mixed use of propofol

remifentayl. Dovepress.2014;176(3)

• Conclusion: In health patient with orthopedic surgery, tiva

with simplified infusion rate of propofol -remifentanyl mixture
allowed satisfactory course of anesthesia fast awaking and
effective postoperative analgesa better than inhalational
techniques

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KPD TIVA (Ketofol and Dex)
Mixture in 1:1:1 Dose for TIVA

• Combination of all these drugs permit lower

dose of each individual agent for TIVA, rapid
recovery and reducing their adverse effects

• Excellent analgesia and anesthesia

T. Chokshi 2019

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Journal Articles...
• Effects of propofol-base TIVA on gastric cancer: a retrospective
study Xiaoyu Zheng. et.al 2019.

• These results indicate that TIVA may be associated with improved

survival in gastric cancer patients who undergo resection.

• Current Systematic Review & Meta analysis suggested that TIVA is

associated with lower all cause mortality after cancer surgery.
Zhaosheng Jin; 2020;11(3):83-94

• TIVA in ERAS/ERPs was understuding, but theoretically best option.

G. Joshi 2018
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 HOW TO GIVE TIVA

1. Single Syringe TIVA (SSTIVA)

2. Manually Controlled Infusion (MCI)

3. Target Controlled Infusions (TCI)

4. Automated (ATIVA ) /Closed Loop Systems

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 1. Single Syringe TIVA
• Only one syringe is used, with the
advantage of dose titration at a single level
& fixed dose mixtures

• Short procedures can be managed with

intermittent boluses, without a syringe
pump.

• It can be practiced in low set ups, and 21

NORA
 2. Manually Controlled Infusion (MCI)

• Manual dosing with fixed infusion rate

• Regular syringe pump can be used to deliver

pre-calculated doses
• Bristol model: Propofol (10-8-6) rule
 Bolus: 1mg/kg plus
 10 mg/kg/hr for 10 minutes,
 8 mg/kg/hr for next 10 minutes,
 6 mg/kg/hr there after
 Opioids or Opioid free Tiva (MMA)
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Ketofol +Dexmed (OFA)
• Dilute ketodex in (2mg/ml + 2ug/ml)

• Loading = 0.5-1ml/kg over 10'

• Maintenance = 0.25 ml/kg/hr

• Don't Adjust analgesic dose

• Depth Can adjust with propofol infusion only

• Switch Off 15' prior to complete of surger

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 NB: Fundamental rule for dilution is minimum conc should be 2mg/ml
With Opioids -MCI
Remifentanyl MCI Fentanyl MCI
• Bolus 2-3 μg/kg over 30
• Initial dose of 1 ug/kg sec
bolus • Followed by 2 μg/kg/hr
• * Maintenance 0.25-0.5 for 30 min
ug/kg/min IV • 1.5 μg/kg/hr from 31-
150 min
• Post-Op 0.025-0.2 • 1 μg/kg/hr until 30 min
mcg/kg/min IV before skin closure

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3. Target controlled infusion TCI
• A computer assisted drug infusion to achieve a pre set drug
concentration in the plasma or the effect site
• User is defining a desired conc- of drug rather than an infusion
rate.
• User interface to enter details and target blood conc.

• Software with pk model, validated for specific drug to control

infusion rate

• The rates necessary to reach and maintain that conc. are

calculated by the syringe pump using an algorithm based on a
three-compartment pharmacokinetic model. 25
A. Nimmo 2019
Part of TCI Pump

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TCI= vaporizer of TIVA

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TCI models
Models Fixed Variable Parameter
parameter parameter
Marsh All rates are V1,V2,V3 Weight
(plasma constant
targeted)
Schnider V1=4.7, V3 V2 k12 k21 Age, LBM,
(effect site ) k13 k31 k10 Sex

Kataria All rates are V13 k10 Weight

(plasma constant except
targeted) k10
Pedfusor All rates are V13 Weight
(effect site ) constant
Minto For remifentanyl, can be used in Cet mode
Allometric A new model (PK/PD) developed using BSI 28
(Eleveld) for diverse populations
Choice of TCI model
• Currently, there is no evidence to support the use of one model
in preference to another and all have proved reliable in clinical
practice.

• All models have similar limitations in terms of the accuracy

and stability of predicted plasma and effect-site concentrations.

• Determinant factors: programming available infusion devices,

age, and physical status of the pts.

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Selecting TCI Targets
• Highly effective drug synergy allows the choice of high
propofol/low remifentanil effect-site concentrations or the
converse to achieve a desired clinical effect.

• Recommended minimum effect-site propofol concentration of

2 - 3 μg/ml is maintained.
• Remifentanil effect-site conc. 1-2ng/ml

• Allowing remifentanil to equilibrate at the effect-site before

starting the propofol is a useful technique with risks and
benefits-
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Checklist for setting up TCI: SIVA 2019
• Use only dedicated pk TCI
pumps
• Ensure that you are trained in
use of the chosen model
• Ensure the pumps are plugged
and charged
• Ensure that the drug dilutions
are correct
• Ensure that the correct syringe
type and size data are entered
and mounted correctly
• Ensure that the pump is
programmed for the drug actually
attached to it
• Ensure that the low and high
infusion pressure alarms are set
• Ensure that the correct patient data
are entered
• Consider if the targets set are
appropriate to the patient's status
• What is plan B if the pump(s) fail?
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4. Closed Loop / AutoTIVA
• Ideal means of automated drug delivery

• The Input – Drug delivery (etc. Propofol, Opioids)

•
• The Output – Evoked Potential, BIS, and vital signs

• Any given moment at input to the systems is function of previous output (measurable
feedback signal)

• Use Newly developing drugs; Hyptiva ( Anesthetic + Narcotic ), Duzitol ( Anesthetic

+ Narcotic + Muscle Relaxant), and Remimizolam ( Narcotic + Benzodiazepine )

• icontrol RPR (Remi- prop-Relaxant)

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T.Choski 2019; Eleveld et.al. (Anesth.2019)
Guideline for safe practice of TIVA

• A.Nimmo.et.al. joint guideline from ASA and SIVA. (2019)

Recommendations (10) next slide
• Principles of TIVA practical aspects: Use TCI; Advanced PK
Model for TCI and Understanding of CSHT facilitate increase
use of TIVA in various clinical settings .
• Al.Rifai.et.al 2016. BJA Educ.16(8). 276-80

 Different TIVA Societies: www.eurosiva.eu, www.worldsiva.org,

https://siva.ac.uk

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Monitoring in TIVA
1. Clinical judgements: response to noxious

2. Tiva trainer pk software

 predict the necessary effect-site conc. real time
3. Use of processed EEG:

4. BIS & TOF If Neuromuscular paralysis

www.eurosiva.eu

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TIVA IN DIFFERENT GROUP OF PATIENTS

• TIVA IN PEDIATRICS PATIENT

• MCI remain an important option • TIVA IN OBESE PATIENTS
• The Kataria and Paedfusor model • The recommended drug dose always
used lower than non-obese patients,
• As far as avoid TIVA In Neonates • Aways secure airway to avoid
respiratory depression with nasal or
oral airways
• Opioid free anesthesia
• TIVA IN GERATRICS
PATIENTS • TIVA IN CRITICAL PATIENTS
• There are no specific protocols
• Dose can be adopted, require a lower
• Less effects on cognitive function, concentration
Cardiopulm. depression • Multi Para monitoring and Oxygen in
• Always start with a low all cases
concentration/infusion rate and slowly
work upwards. T. Chokshi 2022, Egan et.al (2017)
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TIVA during covid-19
pandemic
• TIVA during covid-19 pandemic is far more
advantageous D. Gahlot 2022

• It Avoids deleterious effects of

immunosuppression and lack of respiratory
irritation, thus it providing edge of current
situation
• GAS= Gas Always Side-effects!
T. Chokshi 2020
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TIVA in low resource setup
• Opioids free anesthesia (OFA)
• Mixture of anesthetics + adjuvants
• The purpose is sympathetic block (perfect
anesthesia!)

• No TCI devices (single dose-dependent injection

and/or manual control infusion)

• E.g: ketamine/ ketofol + IV lidocaine +MgSo4 37

combination shows greater HD stability
Potential problems with TIVA
• Propofol related infusion syndrome: (rarely)
• evidence to support this view is very limited.
• Awareness Under Anesthesia mainly dueto
• Technical errors and poor application of knowledge
• 75% of these causes would have been preventable
• Deployment of a processed EEG device especially if muscle
relaxants were given

• Opioid induced hyperalgesia!

NICE & NAP5 (2019) recommendation

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 Future of TIVA Work Station
• Auto TIVA (Work with concept of
Augmented reality of Artificial
Intelligence with help of TCI and BIS)

• Use Different TCI models

• Like Vaporizers, the Syringe Pumps

and TCI systems integrated into the
Anesthesia Work Station
• In built internet, NFC & BT

• Smartphone applications & Remote

controller!

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Summary
TIVA is viable, modern and safe anesthesia, with lots of
advantages

TCI pumps and advance monitors make TIVA easy and

precise

Ketofol is most common drugs used as combined and

also with other drugs

The newer TIVA agents with favourable pk properties

have made TIVA feasible in a wide array of varying 40
clinical scenarios and anaesthetic demands
WINNER!

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REREFERENCES
• A. Nimmo.et.al 2019

• Miller Anesthesia 9 ed

• Stoelting’s . Basic anesthesia 6 ed

• T.Chokshi. TIVA 2022

• NICE & NAP5: TIVA (2019)

• TIVA Journal articles

• Tiva society: www.eurosiva.eu 42